Involvement of Munc18 isoforms in the regulation of granule exocytosis in neutrophils

Cristiana Brochetta, Francesca Vita, Neeraj Tiwari, Lisa Scandiuzzi, Maria Rosa Soranzo, Claudine Guérin-Marchand, Giuliano Zabucchi, Ulrich Blank

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29 Scopus citations

Abstract

Human neutrophil granule exocytosis mobilizes a complex set of secretory granules. This involves different combinations of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins to facilitate membrane fusion. The control mechanisms governing the late fusion steps are still poorly understood. Here, we have analyzed SNARE-interacting Sec1/Munc18 (SM) family members. We found that human neutrophils express Munc18-2 and Munc18-3 isoforms and that Munc18-2 interacts with the target-SNARE syntaxin 3. Munc18-2 was associated preferentially with primary granules but could also be found with secondary and tertiary granules, while Munc18-3 was majorily associated with secondary and tertiary granules. Ultrastructural analysis showed that both Munc18-2 and Munc18-3 were often located in close proximity to their respective SNARE-binding partners syntaxin 3 and syntaxin 4. Both isoforms were also found in plasma membrane fractions and in the cytosol, where they associate with cytoskeletal elements. Upon stimulation, Munc18-2 and Munc18-3 redistributed and became enriched on granules and in the plasma membrane. Munc18-2 primary granule exocytosis can be blocked by introduction of Munc18-2-specific antibodies indicating a crucial role in primary granule fusion. Our results suggest that Munc18-2 acts as a regulator of primary granule exocytosis, while Munc18-3 may preferentially regulate the fusion of secondary granules.

Original languageEnglish (US)
Pages (from-to)1781-1791
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number10
DOIs
Publication statusPublished - Oct 1 2008

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Keywords

  • Exocytosis
  • Neutrophils
  • SM proteins
  • SNARE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Brochetta, C., Vita, F., Tiwari, N., Scandiuzzi, L., Soranzo, M. R., Guérin-Marchand, C., ... Blank, U. (2008). Involvement of Munc18 isoforms in the regulation of granule exocytosis in neutrophils. Biochimica et Biophysica Acta - Molecular Cell Research, 1783(10), 1781-1791. https://doi.org/10.1016/j.bbamcr.2008.05.023